Question

Given below are two statements, one is labelled as Assertion (A) and other one labelled as Reason (R).
Assertion (A) : The free histidine is a dominant buffering system at physiological pH than the protein-bound or dipeptide histidine.
Reason (R) : In proteins or dipeptides, the imidazole pKa decreases substantially-in combination with other amino acids- to a level which is more than 1 pH unit removed from intracellular pH.

• A. Both (A) and (R) are true and (R) is the correct explanation of (A).
• B. Both (A) and (R) are true but (R) is NOT the correct explanation of (A).
• C. (A) is true but (R) is false.
• D. Both (A) and (R) are false.

Hint:

Free histidine has a low concentration in cells and a pKa of 6.0. When bound in dipeptides like carnosine, its pKa increases to 6.83, making it an excellent buffer in muscle and nerve tissues.

Answer 1

The Correct Option is D

Step 1: Understanding the Concept:
Histidine is an amino acid containing an imidazole ring side chain.
The pKa of the imidazole group in free histidine is approximately 6.0, which is near physiological pH, allowing it to act as a weak acid or base to resist pH changes.

Step 2: Detailed Explanation:
Let us analyze both statements individually:
- Assertion (A) is false: Free histidine is present at very low concentrations within cells.
Instead, it is the protein-bound histidine residues (such as in hemoglobin) and histidine-containing dipeptides (such as carnosine and anserine) that are highly abundant in tissues.
These protein-bound and dipeptide forms serve as the dominant intracellular buffering systems at physiological pH, not free histidine.
- Reason (R) is false: When histidine is incorporated into proteins or dipeptides, the local molecular environment can shift the pKa of its imidazole group.
This shift does not universally decrease the pKa.
In many proteins and dipeptides like carnosine (beta-alanyl-L-histidine), the pKa of the imidazole ring shifts upward (to around 6.8–7.0).
This brings the pKa closer to the physiological intracellular pH ($\approx 7.2$), enhancing its chemical buffering capacity.
It is incorrect to state that the pKa decreases substantially to more than 1 pH unit away from physiological pH.
Therefore, both Assertion (A) and Reason (R) are false.

Step 3: Final Answer:
Both Assertion (A) and Reason (R) are false.